Investigations of laboratory animals are designed to relate altered plasma glucose, lipid and insulin concentrations observed in pregnancy to specific actions and interactions of placental hormones on the metabolism of skeletal muscle, liver and adipose tissue. Additional studies will delineate relative effects of natural and synthetic estrogens on these parameters. It is also the aim of these projects to establish how placental hormones and pregnancy may modify glucagon as well as insulin secretion by the isolated pancreatic islet and to what extent these changes represent a direct influence of the hormones on islet physiology. In proposed clinical studies plasma glucagon and insulin response patterns of normal, obese and diabetic subjects will be assessed following specific oral and intravenous challenges. Similar investigations are contemplated in individuals who are pregnant or receiving natural and synthetic sex steroids. These measured parameters will be related to carbohydrate and lipid alterations that attend these conditions.